{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T15:03:35Z","timestamp":1784300615735,"version":"3.55.0"},"reference-count":79,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:00:00Z","timestamp":1772928000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:00:00Z","timestamp":1772928000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100011025","name":"Government of Western Australia","doi-asserted-by":"publisher","award":["2021\/GR000223"],"award-info":[{"award-number":["2021\/GR000223"]}],"id":[{"id":"10.13039\/501100011025","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HIV Medicine"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Mutations in human immunodeficiency virus type 1 (HIV\u20101) enable the virus to evade recognition and killing by human leucocyte antigen (HLA)\u2010restricted T cells. These viral adaptations are specific to the HLA type of individuals and are therefore evident as HLA allele\u2010HIV sequence associations at the population level. Most studies of HLA associations have been cross\u2010sectional and may not capture selective changes that have accumulated to reach fixation at the population level, with potential impacts on viral replication and clinical outcomes. In this study, we examined the population from Western Australia, where HLA\u2010HIV\u20101 associations were first demonstrated, to determine if ongoing evolution has occurred over more than 30\u2009years of observation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Cross\u2010sectional HIV\u20101 subtype B sequences sampled at two time points, early in the epidemic (1992 \u2013 2002,\n                      <jats:italic>n<\/jats:italic>\n                      =\u2009182) and recently (2017 \u2013 2022,\n                      <jats:italic>n<\/jats:italic>\n                      =\u2009119) was utilised to examine HIV\u20101 evolutionary dynamics overtime. In addition, HIV\u20101 subtype B viral load records (one measurement per individual) from a five\u2010year period early in the epidemic (1997 \u2013 2002,\n                      <jats:italic>n<\/jats:italic>\n                      =\u2009673) were compared with recent data (2017 \u2013 2022,\n                      <jats:italic>n<\/jats:italic>\n                      =\u2009363) to determine whether any population level HIV\u20101 adaptation has functional impact.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The analysis identified 120 amino acid positions across the Gag, Pol and Nef genes that showed significant change in proportion over time, with most (100\/120; 83.3%) showing an increase in the proportion of one or more of the non\u2010consensus amino acids. Of these positions, 35% (42\/120) included one or more amino acids (48; 34 in Pol, 9 in Gag and 5 in Nef) reported as HLA\u2010associated viral adaptations (35\/48; 72.9%) or putative compensatory adaptations (11\/48, 22.9%). Over two thirds of these adaptations (68.8%; 33\/48) increased in proportion over time (range 5.8% to 46%), with eight becoming the consensus sequence. We also observed the accumulation of specific compensatory mutations within epitopes presented by protective HLA alleles. Other accumulated non\u2010consensus amino acid changes (38\/120) were predicted to weaken the peptide\u2010HLA binding affinity of known HIV T cell epitopes, suggesting that the previously published list of HLA\u2010associated viral adaptations used in our study was not exhaustive. Only two Pol reverse transcriptase non\u2010nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations showed a significant change in proportion over time (K256Q [K101Q in reverse transcriptase region]; 22.9%, P\u2010adjusted &lt;0.001 and K258N [K103N in reverse transcriptase region]; 7.7%, P\u2010adjusted\u2009=\u20090.020). Notably, we highlight the significant accumulation of adaptations (Gag: R76K, 40.8%, P\u2010adjusted &lt;0.001; H219Q, 25.8%, P\u2010adjusted\u2009=\u20090.020 and R286K, 24.4%, P\u2010adjusted\u2009=\u20090.036) that confer adaptation to both HLA\u2010restricted T cell immune responses and antiretroviral therapy. There was a significant increase in baseline viral load between the two time periods examined (\n                      <jats:italic>P<\/jats:italic>\n                      \u27e80.001, OR\u2009=\u20092.4).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings provide evidence of ongoing HIV\u20101 adaptation to human immune responses at the population level, with a likely increase in virulence, as captured by viral load. The enrichment of viral adaptations within circulating strains may lead to loss of immune targets for prevalent immune responses and has important implications for vaccine development and cure strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/hiv.70215","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T10:34:56Z","timestamp":1772966096000},"page":"918-934","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The impact of accumulating immune adaptation in circulating strains of\n                    <scp>HIV<\/scp>\n                    \u20101"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4228-8765","authenticated-orcid":false,"given":"Marwah","family":"Al\u2010kaabi","sequence":"first","affiliation":[{"name":"School of Human Sciences University of Western Australia  Perth Western Australia 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